Our work on the effects of dextroamphetamine in normal twins and euthymic patients with bipolar affective disorder has been largely completed. A heritable excitation response to amphetamine is predictable by baseline variables of high MHPG, low prolactin and low pulse, and is correlated with post-drug rise in cortisol. The excitation response may be blocked by haloperidol, suggesting a role for dopamine. Neither this response nor other heritable responses, however, separate bipolar patients from controls; thus, amphetamine response is unlikely to be useful as a genetic marker for affective disorder. Beta-endorphin response to amphetamine has been found to correlate with cortisol response; this may indicate simultaneous release of these substances in man. Cholinergic agonist studies are being pursued using pilocarpine and arecoline as the stimulating agents in patients and normal control twins.